Growth and function of human parathyroid tissue transplanted to athymic mice

The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.     

Monte Carlo simulation of a miniature, radiosurgery x-ray tube using the ITS 3.0 coupled electron-photon transport code

A miniature, interstitial x-ray generator has recently been developed and is currently undergoing clinical trials for the treatment of brain tumors. The maximum photon energy from this x-ray tube is 50 keV, although most of the initial testing has been carried out at 40 keV. Dose rates of up to 2 Gy/min in a water phantom at a distance of 10 mm from the tube tip are produced. In this paper we describe the modeling and simulation of x-ray production from this device using the ITS 3.0 Monte Carlo code. Verification of the simulation of x-ray production in the device was carried out by comparing predictions of spatial photon distribution, energy spectrum, and dose versus depth in water with experimentally obtained measurements. Agreement between the simulated results and experimental measurements was fairly good when comparing the angular distribution of photons emitted from the x-ray tube and very good when comparing dose rate versus depth in a water phantom. Discrepancies observed when comparing the calculated and measured estimates of characteristic line radiation were reduced by incorporation of a modification to the ITS code. Possible causes of the remaining discrepancy in bremsstrahlung intensity are discussed.     

Development of technologies aiding large-tissue engineering

Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors.     

Down modulation of MHC surface molecules on B cells by suppressive immune complexes obtained from chronic intestinal schistosomiasis patients

The effect of repeated maximal isometric knee extensions on electromechanical delay (EMD) and associated muscle temperature changes were investigated on seven college aged subjects. The exercise produced a significant reduction in muscle contraction force, rate of force development and muscle conduction velocity, whilst the muscle temperature increased by 2.1 degrees C. The EMD increased from a pre-exercise value of 38.4 (SEM 3.4) ms to 55.7 (SEM 3.4) ms post-exercise. In an attempt to evaluate the effect of muscle temperature on EMD, hot and ice-water bags were placed on the quadriceps muscle to alter muscle temperature. The EMD in isometric maximal knee extension was measured at 38, 36, 34, 32 and 30 degrees C. The results showed that the EMD elongated at muscle temperatures either lower or higher than 36 degrees C. It was speculated that the increased muscle temperature might contribute to 20-25% of the EMD elongation found during the fatiguing intermittent exercise. The information of the effects of muscle temperature on EMD could be useful when evaluating the effects of strenuous exercise, in which a substantial muscle temperature change might occur, on the time delay between myoelectrical activity and force generation.     

Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Controlling bacterial contamination of an enteral formula through the use of a unique closed system: contamination, enteral formulas, closed system

Contamination of enteral diets may play an essential role in formula tolerance and safety for patients. Contaminated enteral formula commonly support microbiological growth. Commercially sterile liquid formulas received from the manufacturer are required by the Food & Drug Administration (FDA) to be shelf-stable and free from enteric pathogens. This study examined the use of large volume, closed system containers in a typical nursing home. Large volume (1500 mL) containers with unique pierceable caps and piercing spikes were studied to determine their ability to reduce the incidence of microbiological contamination due to their design and ability to decrease handling requirements. This study took place in a room of a typical nursing home. In this clinical setting, 211 containers and administration spike sets were evaluated following a 36-h hangtime. Contamination was virtually nondetectable. Nursing staff in a clinical facility can effectively utilize a large volume, prefilled, ready-to-use feeding system to achieve delivery of noncontaminated product for up to 36 h hangtime.     

Family psychosocial screening: should we focus on high-risk settings?

The objective of this study was to address the question of whether or not psychosocial screening should be focused on "high-risk" populations. A cross-sectional survey of mothers of young children was conducted in various clinics: 758 in teaching clinics, 444 in private practices, and 202 at a military clinic. The self-administered questionnaire covered demographic factors, problems in mothers family of origin, maternal depression, and substance abuse. Mothers in the teaching clinics were younger and had less education and lower incomes than mothers in private practices, with intermediate levels in the military clinic. However, a substantial proportion of mothers seen in all sites reported psychosocial problems. Approximately 20% of mothers in all sites reported a family history of alcoholism. Positive screens for maternal depression ranged from about 15% to 35%. Binge drinking was reported by 10% to 20% at different sites. Psychosocial problems were common even among families seen in "low-risk" settings. Focusing screening only on high-risk clinics would miss many families with psychosocial problems.     

Absorption of di-linoleoylphosphatidylcholine after oral administration

Essentiale and Lipostabil contain "essential" phospholipids from the soybean, mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is considered as the main active ingredient. A single oral dose of d15-DLPC loaded with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1-position was given to volunteers. Sera from 11 blood samples taken within 48 h after application were examined by means of mass spectrometry with regard to d9-choline and d6-linoleic acid in the 1- and 2-position of serum phosphatidylcholines (PC) as well as in the serum triglycerides. d9-choline, i.e. the total of d15-PC and d9-PC, showed maximum values of 5.6% of the total serum PC concentration. Normally, about 1.3% of PC in the human serum is DLPC. Serum 1-linoleoyl-PC was increased by 32-40% after oral application of d15-DLPC. A minor uptake of d6-linoleic acid into the 2-position of serum PC, which is rich in linoleic acid, and into the serum triglycerides was observed with peak values of 2.3% and 6.1%, resp. The uptake of polyunsaturated PC species like DLPC and 1-linoleoyl-PC into the liver after oral application of drugs containing such species in high amounts like "essential" phospholipids with about 50% of DLPC let expect therapeutic effects on membranes into which this special species is incorporated.